The nature of the signal that controls stress induced remodeling activity of bone remains unknown despite extensive investigations during recent years. Among the mechanisms proposed, fluid flow in bone is thought by many investigators to be a key factor that may affect cells directly by pressure or nutritional effects, or Indirectly by production of stress generated potentials (SGPs) via the electrokinetic phenomenon known as streaming. Although several investigators have studied behavior of fluids in stressed bone in vitro, and streaming potentials are thought to originate in bone porosity in the size range of 200-800A, little is known of the role of the intracortical vasculature or of other structural, biological or biochemical factors which may modulate fluid flow and SGPs in vivo. Our goal is to define these factors as a step toward predicting the electromechanical micro-environment of cells in stressed bone in vivo, and determining the biologic significance of SGPs with reference to bone remodeling in normal and disease states. In Phase 1 of the project, we will measure SGPs in vitro as a function of frequency (0.1-40Hz) in relation to thickness, permeability, and porosity of a bone sample that is progressively thinned. Results will indicate how intracortical vascular channels affect the relaxation of fluid flow and SGPs, and will aid in development of predictive models. In Phase II, we will accomplish a unique quantitative study on living canine bone in which SGPs will be generated (0.4-40 Hz) in the tibia of each anesthetized animal by a specially designed servohydraulic loading system coupled directly to the bone. All SGP recording will employ a new type of Ag.AgCl electrode of our own design that permits data acquisition from a circumscribed and identifiable site and greatly improves repeatability. Thus, measurements in vivo will be followed by sequential measurements from the same site in vitro, and the results will be correlated with mechanical strain, permeability and histomorphometric data on the same location. Using the in vivo preparation, we shall determine first how physical chemical changes may cause SGPs In vitro to differ from those measured in vivo in order to relate the background of existing in vitro studies to physiological conditions. Following this, we shall investigate additional factors such as structural changes in vasculature, electrolyte composition, and biochemical agents which may alter fluid flow or the zeta potential, thus modulating SGPs and the cell environment in living bone during dynamic mechanical stress.